First-line immune checkpoint inhibitors alone or in combination with chemotherapy in real-life elderly patients with advanced non-small cell lung cancer (NEJ057).
Authors: Mao Uematsu, Yoko Tsukita, Takehiro Tozuka, Kohei Kushiro, Shinobu Hosokawa, Toshiyuki Sumi, Osamu Honjo, Ou Yamaguchi, Tetsuhiko Asao, Jun Sugisaka, Go Saito, Jun Shiihara, Ryo Morita, Seigo Katakura, Takehiro Yasuda, Kakeru Hisakane, Eisaku Miyauchi, Satoshi Morita, Kunihiko Kobayashi, Hajime Asahina
Journal: Journal of Clinical Oncology (2023)

9012 Background: Immune checkpoint inhibitor (ICI) plus chemotherapy is now a standard treatment for non-small cell lung cancer (NSCLC) without targetable oncogene alternations. However, the efficacy and safety of ICI plus chemotherapy (ICI-chemo) in 75 years or older patients have not been elucidated. The aim of this study is to reveal the real-world choice of first-line drugs in elderly patients (pts) and evaluate the efficacy and safety of ICI-chemo. Methods: We conducted a multicenter (58 centers in Japan), retrospective cohort study of consecutive 75 years or older pts with clinical stage IIIB, IIIC, IV, postoperative or radiotherapy recurrent NSCLC who started first-line systemic therapy between December 2018 and March 2021. Pts with epidermal growth factor receptor mutations, anaplastic lymphoma kinase rearrangements, or whose first-line systemic therapy was molecular targeted therapy were excluded. Results: A total of 1245 pts were enrolled: median (range) age 78 (75-95) years; 278 (22%) female; 367 (29%) ECOG PS 0, 680 (55%) PS 1 and 171 (14%) PS 2; 678 (54%) adenocarcinoma; PD-L1 tumor proportion score 268 (22%) &lt;1%, 387 (31%) 1-49% and 410 (34%) ≥50%; 354 (28%) ICI-chemo, 425 (34%) ICI alone, 311 (25%) platinum-doublet chemotherapy and 155 (12%) single agent chemotherapy. The median overall survival (OS) was 20.0 months (95%CI, 17.1–23.6) in the ICI-chemo group, 19.8 months (95%CI, 16.5–23.8) in the ICI alone group, 12.8 months (95%CI, 10.7–15.6) in the platinum-doublet chemotherapy group and 9.5 months (95%CI, 7.4–13.4) in the single agent chemotherapy group, respectively. After propensity score matching, there was no difference in OS and progression-free survival (PFS) between ICI-chemo group (n=96) and ICI alone group (n=95) in PD-L1 ≥1% (OS: HR, 0.98; 95% CI, 0.67-1.42, PFS: HR, 0.92; 95% CI, 0.67-1.25). Regardless of PD-L1 subgroups (1-49% or ≥50%), no significant differences in OS and PFS were observed. Concerning safety, Grade 3 or higher immune-related adverse events (irAEs) occurred in 86 pts (24.3%) in the ICI-chemo group and 76 pts (17.9%) in the ICI alone group (p = 0.03). The number of pts who required steroids for irAEs was 115 (32.5%) in the ICI-chemo group and 105 (24.7%) in the ICI alone group (p = 0.02). Pneumonitis was reported in 83 pts (23.4%) in the ICI-chemo group and 66 pts (15.6%) in the ICI alone group (p = 0.006). Conclusions: In real-world data for pts aged 75 years or older, ICI-chemo did not improve survival and increased the incidence of grade 3 or higher irAEs compared to ICI alone. Based on our results, ICI alone is recommended for elderly pts with PD-L1 positive NSCLC. Clinical trial information: UMIN000046700 .